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12/6/2018

Biopharma/Investing
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Samsung Biologics has been halted for 3 weeks? These accounting issues have been persistent and the stock did fine. I wonder what is going on in Korea.

Papers I’ve Read
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Isosteric analogs of lenalidomide and pomalidomide: Synthesis and biologic activity. Ruchelman, Muller, et al. Bioorg & Med Chem Lett 2013.
Not the world’s most impressive SAR paper, but exploring the decorations of the indole (phthalimide) and glutarimide moieties led to little improvements. Of course, the only measured changes were TNF response to LPS, IL-2 increase and cell line anti-proliferative effect. At the time, cereblon was already identified as the therapeutic target for the “IMIDs” so it is a bit surprising to see these assays. Also, the “isosteres” aren’t very creative. 4-CH3 improves Revlimid but ethyl does not and other, longer variants were not attempted.

tp53-dependent and independent signaling underlies the pathogenesis and possible prevention of Acrofacial Dysostosis – Cincinnati type. Watt et al. Hum Mol Genet 2018.
This ultra-rare disorder has only been described in a few humans. A ribosomopathy, I’m not sure if its embryonic lethal in all homozygotes or some hypomorphic alleles are compatible with life, or what. This one is caused by a mutation in a RNA Pol I subunit, creating the fundamental and ubiquitous ribosome. Despite that, the pathogenesis is very tissue-specific. It was exciting to read tp53 -/- somewhat ameliorates the POLR1A -/- phenotype but it doesn’t rescue it completely. This CCH group also discovered and named the first patients with the illness. I find it incredible how quickly progress can be made in these ultra-rare/newly discovered illnesses.

Exploring the speed limit of toehold exchange with a cartwheeling DNA acrobat. Li et al. Nature Nanotechnology 2018.
I don’t know anything about engineering but how this DNA literally cartwheels (while one strand is bound to the “floor”, the other strand moves end-over-end to move its free-end to bound again) is fairly incredible. Still, don’t expect DNA nanomachines fixing up your cells anytime soon.

Personal
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7 days in and my tooth is still killing me. All that anyone can talk about here is Meek Mill’s new album.

Ehhhh, i’d be cautious in calling a phthalimide an indole (or indole-derivative). Perhaps an isoindole derivative (as this at least puts the NH group at the correct position), but this is a fairly unstable compound.

More accurate to say that phthalimides are derivatives of phthalic anyhydrides. The conversion from phthalic anhydrides to phthalimides is very straight forward. RIP to these authors if they decided to use indole as a starting material.